The goal of the CBI Training Program is to provide students with the intellectual and technical skills that are necessary to solve important and complex biological problems that can be most effectively addressed by studies at the chemistry-biology interface. We are focusing on the mechanistic chemistry of biomolecules that have implications for impacting human health and treatment of disease. This is a theme that is of interest to a significant population of students on campus and serves as an excellent system for the application of tools at the chemistry-biology interface to solve important biological problems. The program creates a group of chemists and biologists who can speak the same language and thereby function effectively in multidisciplinary teams. The Program involves 34 participating faculty from two separate Schools within the University of Pennsylvania, The Perelman School of Medicine (SOM) and The School of Arts and Sciences (SAS). Participating students come primarily from two graduate groups that span institution and school boundaries, the Graduate Group in Chemistry (CHEM, in SAS) and the Graduate Group in Biochemistry and Molecular Biophysics (BMB, in SOM). To ensure that students carry out research within the scope of the training program, students are selected for the program after they have chosen a thesis laboratory and project and generally in their second year. To ensure chemistry-biology interface training and cross-fertilization between the chemistry and biology students that participate in the program, students participate in the following activities: (1) research at the chemistry-biology interface, (2) didactic course-work dealing with the chemistry and biology of proteins, nucleic acids and small biomolecules, including a literature-based component, (3) an annual student-run Chemical Biophysics mini-symposia series, (4) twice monthly student luncheons, (5) an annual Chemistry-Biology Interface retreat, (6) an annual mid-Atlantic Frontiers at the Chemistry-Biology Interface Symposium, and (7) a structured career development plan. The program also has effective mechanisms in place for the recruitment and retention of underrepresented minorities as well as the disadvantaged and disabled, and for student instruction in the responsible conduct of research. We request funds for a steady state predoctoral training group of ~ 40 students, including 8 who are funded during years 2 and 3. Oversite of the Training Program is by the PI, Ronen Marmorstein and Co-PI, E. James Petersson, with input from CHEM (SAS) and BMB (SOM) External Advisory Committees and Internal CBI Training Committee, comprised of roughly equal faculty representation from the two participating schools and trainee representatives, which meets every 6 months. The CBI Training Committee votes on the selection of students for funded training slot positions, ensuring equitable distribution of students, encouraging applications from underrepresented minorities, the disadvantaged and disabled and administering other functions of the program.